While most naturally occurring DNA and RNA adopt the now quite familiar double-helix structure, certain sequences can under the appropriate conditions adopt a three-stranded, triple-helical structure. Both intramolecular and intermolecular triplexes have been described. Evidence for the existence of triplex structures in vivo is limited, although cellular proteins have been identified that avidly and specifically interact with such species. The postulated roles of triplexes and the proteins that interact with them in cancer and their potential utility as diagnostic markers are discussed in this review.